We have developed what we consider to be a viable animal model of the role of dopamine in mediating certain of the neurological components of Parkinson's disease. This animal preparation is made by bilaterally injecting 6-hydroxydopamine into the substantia nigra of rats. With the exception of tremor and taking into account obvious differences in the expression of motor behavior due to species differences, our preparation bears considerable histochemical, histopathological, and neurological similarity to the clinical symptomatology seen in human Parkinsonism. We propose to further investigate the behavioral and histochemical properties of this animal model by examining dose-response and time- course effects of intranigrally micro-infused 6-hydroxydopamine on (1) physiologically significant substances in the brain potentially involved in Parkinson's disease (i.e., monoamines, acetylcholinesterase, and monoamine oxidase) and (2) a variety of behavioral processes including sexual behavior, shock-elicited aggresion, food and water intake, quantitatively measured locomotor activity, and a newly developed behavioral technique for the analysis of precise motor responses (lever- positioning). In addition, the effects of drugs known to alter the symptomatology of Parkonsinism will be studied in the bilateral dopamine-lesioned preparation described above. These drugs are L-DOPA, 5-HTP, apomorphine, amantadine, and atropine. Combinations of these drugs will also be studied, and dose-response and time-course relationships will be determined. It is hoped that data will derive from this series of experiments which will not only enlarge our understanding of the role of dopamine in behavior but may also shed light on various characteristics and mechanisms of Parkinson's disease.